Pages

Sunday, February 19, 2017

New technology to speed up testing of cancer drugs

Nottingham: A new technology that could speed up the
testing of drugs and reduce the use of animals in the lab has been
developed by scientists at The University of Nottingham. The researchers in the University’s Division of Cancer and Stem Cells
have designed a device that allows dozens of tiny balls of cells,
called spheroids, to be sliced simultaneously to examine their structure
and function. The method, which is detailed in the academic journal Scientific Reports,
will enable other scientists to more rapidly assess whether new
therapies and tissue engineering are likely to work in the real world,
and could be up to 11 times more efficient than current methods.

Dr Delyan Ivanov
said: “When I started exploring spheroids by slicing them, I was
frustrated by the slow and gruelling nature of the process. I had to cut
spheroids cultured in many different drugs and it was taking me months,
there were many manual steps.
“Inspired by the principle of 3D printing, I decided to design my own
tool for arranging all spheroids from an experiment in the same plane
in a microchip-like pattern in a gel.”

Overcoming limitations

Dr Ivanov, who designed the device during his EPSRC-funded doctoral
prize fellowship (Engineering and Physical Sciences Research Council),
was able to refine the design after enlisting the help of Joseph White, a
research technician in the University’s Additive Manufacturing group,
who printed 20 different versions of the prototype for testing.
The team will now be sharing the design files and methodology openly
with the scientific community to ensure that everyone can immediately
benefit from the technology.
New drugs for cancer and strategies to build tissues from stem cells
have historically been tested in the laboratory in human cells grown as a
‘carpet’ on plastic. In contrast to the natural behaviour in the human
body, the cells in these two-dimensional cultures have limited
interaction with each other and produce little of the natural ‘glue’
called extracellular matrix.
To overcome these limitations, tiny three-dimensional balls of cells
(spheroids) which are smaller than a pinhead, interact more closely with
one another and behave more like their natural counterparts in the
human body are now being used.
Scientists are growing spheroids derived from tumour and normal
tissues and have even developed improved, more organised structures
which resemble organs, called organoids.
The catch was that, while two-dimensional structures can be examined
just by looking down the microscope, the 3D spheroids need to be sliced
into hundreds of thin slices just 0.005mm (5 µm) thick in order to get a
reliable picture of their structure and function.

Reducing animal testing

The Nottingham invention allows researchers to arrange 66 spheroids
grown in the presence of different drugs and molecules and slice
simultaneously and more quickly, allowing scientists to answer more
questions using the same set of laboratory-grown tissues.
Many experiments currently done in animals could be done in these
spheroid and organoid cultures reducing and ultimately replacing some
animal testing in cancer research and tissue engineering.Dr Anna Grabowska,
who mentored Dr Ivanov at Nottingham during his post-doc, added: “We
would like to create cell-based models in the laboratory which closely
mimic the natural behaviour of cells in the human body. We are doing
this not only by culturing cells as spheroids but by including multiple
cell types and the right extracellular matrix. Delyan’s technology would
allow us to monitor the behaviour of laboratory models of human tissues
and organs in a faster, more efficient way.”
The paper being published in Scientific Reports
includes the blueprints of the device, demonstration of the
possibilities of the new technology and offers an instructional video to
show researchers how to make their own spheroid microarrays.